The duration of antigenic stimulation determines the fate of naive and effector T cells.
It is known that T cells engage antigen-presenting cells (APCs) in a stable interaction that results in sustained TCR signaling. We show here that the duration of this process is critical in determining whether T cells will be activated or deleted. Whereas naive T cells require approximately 20 hr of sustained signaling to be committed to proliferation, effector T cells become committed after only 1 hr but die following activation if antigenic stimulation is prolonged. Costimulation by anti-CD28 facilitates T cell activation by decreasing the time of commitment and by protecting T cells from death. These findings explain in quantitative terms the essential requirement for professional APCs in T cell priming and show that the duration of antigenic stimulation is the major factor determining the fate of naive and effector T cells.
Iezzi
G
G
Basel Institute for Immunology, Switzerland.
Karjalainen
K
K
Lanzavecchia
A
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000648:ultrastructure; D018106:CD28 Antigens / Q000276:immunology* / Q000494:pharmacology; D016923:Cell Death / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000648:ultrastructure
D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2